Pediatric patients with childhood acute otitis media determined to be of moderate severity in accordance with the Clinical Practice Guideline for Diagnosis and Management of Acute Otitis Media in Children (2013, hereinafter referred to as the Guideline).

Classification by specialty

Oto-rhino-laryngology

Classification by malignancy

Others

Genomic information

NO

Objectives

Narrative objectives1

Investigation of the efficacy and safety of treatment with amoxicillin alone or in combination with clarithromycin in pediatric patients with moderate childhood acute otitis media

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Assessment

Primary outcomes

(1) Efficacy evaluation (scoring for the severity of acute otitis media)
The endpoints are the percentages of patients who show a complete response or partial response and patients who show a complete response, partial response or no change among all patients for efficacy evaluation. For the percentages, 95% confidence intervals will be calculated. The percentage of patients who show a complete response or partial response among all patients for efficacy evaluation will be compared between the AMPC group and CAM/AMPC group using Fisher's exact test.

(2) Lift reflex
Summary statistics for scores and changes in scores from the start of study treatment until the completion or discontinuation of study treatment will be calculated at designated time points and compared between the AMPC group and CAM/AMPC group using the Wilcoxon rank sum test.

(3) Safety evaluation
The numbers of events, numbers of patients who experience events, frequencies and corresponding 95% confidence intervals will be calculated for all adverse events and adverse events for which the causal relationship to the investigational drug cannot be ruled out. The frequencies of adverse events and events for which the causal relationship to the investigational drug cannot be ruled out will be compared between the AMPC group and CAM/AMPC group using Fisher's exact test. The level of significance is 0.05 for a two-sided test.

Key secondary outcomes

(1)Efficacy evaluation (by the physician)
The endpoints are the percentages of patients who show a complete response or partial response and those who show a complete response, partial response, slight response or no change among all patients for efficacy evaluation. Analyses will be performed using the analysis procedures for primary endpoint (1).

(2) Test of cure
The endpoints are the percentages of patients who are cured and patients who are cured or are not cured among all patients for efficacy evaluation. Analyses will be performed using the analysis procedures for primary endpoint (1).

(3) Evaluation of exacerbation of infection
The endpoints are the percentages of patients who do not experience exacerbation of infection and patients who experience or do not experience exacerbation of infection among all patients for efficacy evaluation. Analyses will be performed using the analysis procedures for primary endpoint (1).

(4) Bacteriological efficacy
The endpoints are the percentage of patients for whom bacterial infection has resolved, appears to have resolved or has partially resolved and the percentage of patients for whom bacterial infection has resolved, appears to have resolved, has partially resolved or has not changed among all patients for efficacy evaluation. Analyses will be performed using the analysis procedures for primary endpoint (1).

(5) Background factors causing acute otitis media to become refractory
For the following, the odds ratios and corresponding 95% confidence intervals will be calculated: young children under 2 years old; detection of drug-resistant bacteria; history of recurrence of otitis media; group childcare; history of treatment with antimicrobial drugs during the previous month; onset of complication of sinusitis; and onset of bilateral diseases.

(6) Follow-up
The time to exacerbation and number of times exacerbations occur will be summarized.

Base

Study type

Interventional

Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Intervention group (clarithromycin/amoxicillin group): amoxicillin is administered for 5 days, and clarithromycin for 3 days.

Interventions/Control_2

Control group: amoxicillin is administered for 5 days

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Eligibility

Age-lower limit

0

years-old

<=

Age-upper limit

5

years-old

>

Gender

Male and Female

Key inclusion criteria

(1) Patients between 28 days and 5 years old at the time informed consent is obtained

(2) Patients determined to have moderate severity acute otitis media in accordance with the Guideline

(3) Patients for whom written informed consent can be obtained from the guardian of the patient

Key exclusion criteria

(1) Patients with a history of hypersensitivity to penicillin-based or macrolide-based antibiotics

(2) Patients with a history of epilepsy or other convulsive disorders

(3) Immunodeficient patients

(4) Patients with maxillofacial growth impairment

(5) Patients determined by the investigator or sub-investigator as ineligible for the present study